Freshly squeezed vaccines

Microfluidic cell-squeezing device opens new possibilities for cell-based vaccines

MIT researchers have shown that they can use a microfluidic cell-squeezing device to introduce specific antigens inside the immune system’s B cells, providing a new approach to developing and implementing antigen-presenting cell vaccines.

Such vaccines, created by reprogramming a patient’s own immune cells to fight invaders, hold great promise for treating cancer and other diseases. However, several inefficiencies have limited their translation to the clinic, and only one therapy has been approved by the Food and Drug Administration.

While most of these vaccines are created with dendritic cells, a class of antigen-presenting cells with broad functionality in the immune system, the researchers demonstrate in a study published in Scientific Reports that B cells can be engineered to serve as an alternative.

“We wanted to remove an important barrier in using B cells as an antigen-presenting cell population, helping them complement or replace dendritic cells,” says Gregory Szeto, a postdoc at MIT’s Koch Institute for Integrative Cancer Research and the paper’s lead author.

Darrell Irvine, a member of the Koch Institute and a professor of biological engineering and of materials sciences and engineering, is the paper’s senior author.

A new vaccine-preparation approach

Dendritic cells are the most naturally versatile antigen-presenting cells. In the body, they continuously sample antigens from potential invaders, which they process and present on their cell surface. The cells then migrate to the spleen or the lymph nodes, where they prime T cells to mount an attack against cells that are cancerous or infected, targeting the specific antigens that are ingested and presented.

Despite their critical role in the immune system, dendritic cells have drawbacks when used for cell-based vaccines: They have a short lifespan, they do not divide when activated, and they are relatively sparse in the bloodstream.

B cells are also antigen-presenting cells, but in contrast to dendritic cells, they can proliferate when activated and are abundant in the bloodstream. However, their functionality is more limited: Whereas dendritic cells constantly sample antigens they encounter, a B cell is genetically programmed only to bind to a specific antigen that matches the receptor on its surface. As such, a B cell generally will not ingest and display an antigen if it does not match its receptor.

Using a microfluidic device, MIT researchers were able to overcome this genetically programmed barrier to antigen uptake — by squeezing the B cells.

Through “CellSqueeze,” the device platform originally developed at MIT, the researchers pass a suspension of B cells and target antigen through tiny, parallel channels etched on a chip. A positive-pressure system moves the suspension through these channels, which gradually narrow, applying a gentle pressure to the B cells. This “squeeze” opens small, temporary holes in their membranes, allowing the target antigen to enter by diffusion.

This process effectively loads the cells with antigens to prime a response of CD8 — or “killer” — T cells, which can then kill cancer cells or other target cells.

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